The albumin in subarachnoid hemorrhage (ALISAH) multicenter pilot clinical trial: Safety and neurologic outcomes

BACKGROUND AND PURPOSE-: Human albumin has been shown to exert neuroprotective effects in animal models of cerebral ischemia and humans with various intracranial pathologies. We investigated the safety and tolerability of 25% human albumin in patients with subarachnoid hemorrhage. METHODS-: The Albumin in Subarachnoid Hemorrhage (ALISAH) Pilot Clinical Trial was an open-label, dose-escalation study. We intended to study 4 different dosages of albumin of increasing magnitude (0.625 g/kg: Tier 1; 1.25 g/kg: Tier 2; 1.875 g/kg: Tier 3; and 2.5 g/kg: Tier 4). Each dosage was to be given to 20 adult patients. Treatment was administered daily for 7 days. We investigated the maximum tolerated dose of albumin based on the rate of severe-to-life- threatening heart failure and anaphylactic reaction and functional outcome at 3 months. RESULTS-: We treated 47 adult subjects: 20 in Tier 1; 20 in Tier 2; and 7 in Tier 3. We found that doses ranging up to 1.25 g/kg/day×7 days were tolerated by patients without major dose-limiting complications. We also found that outcomes trended toward better responses in those subjects enrolled in Tier 2 compared with Tier 1 (OR, 3.0513; CI, 0.6586-14.1367) and with the International Intraoperative Hypothermia for Aneurysm Surgery Trial cohort (OR, 3.1462; CI, 0.9158-10.8089). CONCLUSIONS-: Albumin in doses ranging up to 1.25 g/kg/day×7 days was tolerated by patients with subarachnoid hemorrhage without major complications and may be neuroprotective. Based on these results, planning of the ALISAH II, a Phase III, randomized, placebo-controlled trial to test the efficacy of albumin, is underway.